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Emerging and established modes of cell death during acetaminophen-induced liver injury

Jaeschke, Hartmut ; Ramachandran, Anup ; Chao, Xiaojuan ; Ding, Wen-Xing

Archives of toxicology, 2019-12, Vol.93 (12), p.3491-3502 [Periódico revisado por pares]

Berlin/Heidelberg: Springer Berlin Heidelberg

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Título:
Emerging and established modes of cell death during acetaminophen-induced liver injury
Autor: Jaeschke, Hartmut ; Ramachandran, Anup ; Chao, Xiaojuan ; Ding, Wen-Xing
Assuntos: Acetaminophen ; Acetaminophen - adverse effects ; Analgesics ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; BAX protein ; Biomedical and Life Sciences ; Biomedicine ; Cell death ; Cell Death - drug effects ; Cell Death - physiology ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Cytochrome ; Cytochrome c ; Cytochromes ; DNA fragmentation ; Environmental Health ; Ferroptosis ; Ferroptosis - drug effects ; Ferroptosis - physiology ; Hepatocytes ; Hepatotoxicity ; Humans ; Inflammasomes ; Inflammation ; Inflammatory response ; Injuries ; Iron ; Kinases ; Liver ; MAP kinase ; Membrane permeability ; Mitochondrial permeability transition pore ; Mortality ; Necroptosis ; Necroptosis - drug effects ; Necroptosis - physiology ; Necrosis ; Occupational Medicine/Industrial Medicine ; Oxidants ; Oxidizing agents ; Peroxynitrite ; Pharmacology/Toxicology ; Protein kinase ; Protein kinase C ; Proteins ; Pyroptosis ; Review Article ; Therapeutic applications ; Translocation
É parte de: Archives of toxicology, 2019-12, Vol.93 (12), p.3491-3502
Descrição: Acetaminophen (APAP)-induced liver injury is an important clinical and toxicological problem. Understanding the mechanisms and modes of cell death are vital for the development of therapeutic interventions. The histological and clinical features of APAP hepatotoxicity including cell and organelle swelling, karyolysis, and extensive cell contents release lead to the characterization of the cell death as oncotic necrosis. However, the more recent identification of detailed signaling mechanisms of mitochondrial dysfunction, the amplification mechanisms of mitochondrial oxidant stress and peroxynitrite formation by a mitogen-activated protein kinase cascade, mechanisms of the mitochondrial permeability transition pore opening and nuclear DNA fragmentation as well as the characterization of the sterile inflammatory response suggested that the mode of cell death is better termed programmed necrosis. Additional features like mitochondrial Bax translocation and cytochrome c release, mobilization of lysosomal iron and the activation of receptor-interacting protein kinases and the inflammasome raised the question whether other emerging modes of cell death such as apoptosis, necroptosis, ferroptosis and pyroptosis could also play a role. The current review summarizes the key mechanisms of APAP-induced liver injury and compares these with key features of the newly described modes of cell death. Based on the preponderance of experimental and clinical evidence, the mode of APAP-induced cell death should be termed programmed necrosis; despite some overlap with other modes of cell death, APAP hepatotoxicity does not fulfill the characteristics of either apoptosis, necroptosis, ferroptosis, pyroptosis or autophagic cell death.
Editor: Berlin/Heidelberg: Springer Berlin Heidelberg
Idioma: Inglês

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Emerging and established modes of cell death during acetaminophen-induced liver injury

Jaeschke, Hartmut ; Ramachandran, Anup ; Chao, Xiaojuan ; Ding, Wen-Xing

Berlin/Heidelberg: Springer Berlin Heidelberg

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